DESCRIPTION: The long-term objective is to determine the mechanisms by which the brain influences peripheral immune function and the functional and pathological significance of these changes in immune function. To be tested is the hypothesis that immunoregulatory cytokines synthesized in the brain can influence immune function through secretion into the circulation and by activation of cervical lymph nodes that receive brain extracellular fluid drainage. These mechanisms underlie the acute phase response after stroke and head injury, stress-induced immune inhibition, and CNS infection. To be determined are the relative importance of direct secretion of IL-6 from the brain and of sympathetic nervous systems activation of peripheral immune-competent cells. The PI also proposes to identify which of the known cytokines enter peripheral circulation from the brain and the role of the choroid plexus in their generation. Also to be determined are the effects of established neuropeptides and neurotransmitters on cytokine secretion by choroid plexus and glia. In a separate group of studies, the PI will test the hypothesis that leptin inhibits GH secretion by stimulating hypothalamic release of somatostatin and that the inhibitory effects of leptin on NPY secretion develop over time and are correlated with the appearance of the satiety mechanism in rats.